Asymmetric cell division is a general mechanism of achieving cellular diversity in metazoans and therefore vital to our long-term understanding of development and genetic disease. The somatic gonadal precursors (SGPs) of C. elegans undergo asymmetric cell division, establishing the proximal-distal axis of the gonad. As a result of this asymmetric division, POP-1/TCF is differentially localized in the SGP daughters. The Wnt pathway regulates POP-1 localization, as does components of the cell cycle machinery and the TRA-1/GLI transcription factor. However, the mechanism by which these regulators control POP-1 asymmetry is unknown. The broad goal of this proposal is to understand the molecular mechanisms of how asymmetric cell division is regulated, using the gonad of C. elegans as a model. To this end, the mechanism underlying the control of the Wnt pathway on the asymmetric localization of POP-1 in the SGPs will be determined. A potential role of cell-cell contact in regulating the Wnt pathway will be examined. Finally, use of both forward and reverse genetics methods available in C. elegans will identify new genes that function in asymmetric division, including potential targets of TRA-1/GLI and the cell cycle machinery.